Type IV hypersensitivity

Type IV hypersensitivity
Classification and external resources
MeSH	D006968

Type IV hypersensitivity is often called delayed type hypersensitivity as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response.

CD8+ cytotoxic T cells and CD4+ helper T cells recognize antigen in a complex with either type 1 or 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Type 1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

Examples

Disease	Target antigen	Effects
Diabetes mellitus type 1	Pancreatic beta cell proteins (possibly insulin, Glutamate decarboxylase)	Insulitis Beta cell destruction
Multiple sclerosis	Oligodendrocyte proteins (myelin basic protein, proteolipid protein)	Demyelinating disease Perivascular inflammation Paralysis Ocular lesions
Rheumatoid arthritis	Antigen in synovial membrane (possibly type II collagen)	Chronic arthritis Destruction of articular cartilage and bone
Some peripheral neuropathies	Schwann cell antigen	Neuritis Paralysis
Crohn's disease	Unknown	Chronic inflammation of ileum and colon
Contact dermatitis	Environmental chemicals, e.g. poison ivy, nickel	Dermatitis with usually short-lived itching
Mantoux test* (diagnostic)	Tuberculin	Skin induration indicates TB exposure
Unless else specified in boxes, then ref is: [1] * - Mantoux test not taken from [1]

The pathophysiology of the Tuberculin reaction is explained thus: M. tuberculi are engulfed by macrophages after being identified as foreign, but due to a self- preserving mechanism peculiar to TB it is able to block the fusion of the phagosome within which it is existing with the lysosome which would destroy it. So it can continue existing and replicating within the immune cell designed to destroy it. After several weeks, the immune system somehow [ mechanism as yet unexplained] ramps up and, on stimulation with IFN-gamma, the macrophages become capable of killing M. tuberculi by forming phagolysosomes and nitric oxide radicals. However unfortunately the hyper-activated macrophages secrete TNF which recruits multiple monocytes into the battle. These cells differentiate into epithelioid histiocytes which wall off the infected cells, but at the cost of significant inflammation and local damage.

Some other clinical examples:

• Temporal arteritis
• Hashimoto's thyroiditis
• Symptoms of leprosy
• Symptoms of tuberculosis
• Coeliac disease
• Graft-versus-host disease^[2]
• Chronic transplant rejection

References

1. ^ ^{a b} Table 5-5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
2. ^ "eMedicine - Hypersensitivity Reactions, Delayed : Article by Walter Duane Hinshaw". http://www.emedicine.com/MED/topic1100.htm.